Rapid and effective diagnosis of tuberculosis and rifampicin resistance with Xpert MTB/RIF assay: a meta-analysis

Chang K, Lu W, Wang J, Zhang K, Jia S, Li F, Deng S, Chen M

CRD summary

This review concluded that tuberculosis and rifampicin resistance can be rapidly and effectively diagnosed with the Xpert Mycobacterium tuberculosis/resistance to rifampicin (MTB/RIF; Cepheid) assay. This was generally a well-conducted review but some uncertainty surrounds the reliability and generalisability of the pooled estimates presented and the conclusions seem a little strong.

PubMed and EMBASE were searched to October 2011 for studies published in English. There were no language restrictions. The search strategy was reported. Bibliographies of included studies were searched.

Study selection

Prospective studies of patients with suspected TB and that compared the Xpert MTB/RIF assay with a clearly defined reference standard that was used in all patients were eligible for inclusion. Studies had to report sufficient data to produce 2x2 tables of test performance. The proportion of smear-positive specimens in the included studies ranged from 4.7% to 89.3%. TB incidence ranged from 2.6% to 81.7%. All studies used liquid culture as the reference standard; most also used solid culture. Most evaluations were conducted on pulmonary specimens. All of the included studies were published in 2010 and 2011 (Xpert MTB/RIF was developed in 2008).

Two reviewers independently selected studies for the review; disagreements were resolved by a third reviewer.

Assessment of study quality

Study quality was assessed using the QUADAS tool to award a score out of 14. The authors did not state how many reviewers performed the quality assessment but it appeared to be conducted as part of the data extraction process.

Pooled estimates of sensitivity, specificity and diagnostic odds ratios, with 95% CI, were produced using frequentist meta-analytical methods. Heterogeneity was investigate using Cochran Q and the Ι² statistics; a random-effects model was used where heterogeneity was significant. Pooled estimates of sensitivity and specificity with 95% confidence regions were calculated using the bivariate random-effects model and summary receiver operating characteristic (SROC) curves were produced. Spearman's correlation was used to investigate any threshold effect. Subgroup analysis and meta-regression were used to analyse the sources of heterogeneity (details were not reported in the methods). Publication bias was assessed using funnel plots and Begg’s and Egger’s tests.

Results of the review

Eighteen studies were included in the review. There were 10,224 specimens with suspected TB: 2,983 had microbiologically confirmed TB and 335 had clinically/radiologically diagnosed TB; 9,166 specimens were included in the meta-analysis (range 25 to 4,742 specimens). The median QUADAS score was 12 (range 9 to 14).

Results were provided for HIV coinfection and diagnosing extrapulmonary TB. Full results of the meta-regression analysis were reported.

Authors' conclusions

TB and rifampicin resistance can be rapidly and effectively diagnosed with Xpert MTB/RIF assay.

CRD commentary

The review addressed a clear research question with reproducible inclusion criteria. Relevant sources were searched. Only studies published in English were included. Each stage of the review process was conducted in duplicate, which reduced risks of error and bias. Study quality was assessed using appropriate criteria. The authors produced a summary score for QUADAS (full results were reported in an online appendix) and the overall quality score was used in the analysis. The pooled results reported in the text of the review were those derived from frequentist meta-analytical methods. These analyses were conducted using studies that showed substantial clinical and statistical heterogeneity, therefore their reliability and generalisability was uncertain. When compared to the results of the more robust bivariate model was that used, at least the sensitivity for the diagnosis of RIF was different. Heterogeneity was investigated using appropriate methods.

This was generally a well-conducted review but some uncertainty surrounds the reliability and generalisability of the pooled estimates presented and the conclusions seem a little strong.

Implications of the review for practice and research

Practice: The authors stated that the introduction of Xpert MTB/RIF assay would be helpful for reduction of the infectious pool and improvement in TB control.

Research: The authors did not state implications for research.

Funding

Major Project Chinese National Programs for High Technology Research and Development; Chinese National Natural Science Foundation; National Infectious Disease Prevention and Cure Special Project.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.